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Plasmid-Encoded Interleukin-15 Receptor α Enhances Specific Immune Responses Induced by a DNA Vaccine In Vivo
Journal article   Open access   Peer reviewed

Plasmid-Encoded Interleukin-15 Receptor α Enhances Specific Immune Responses Induced by a DNA Vaccine In Vivo

Kimberly A Kraynyak, Michele A Kutzler, Neil J Cisper, Dominick J Laddy, Matthew P Morrow, Thomas A Waldmann and David B Weiner
Human gene therapy, v 20(10), pp 1143-1156
Oct 2009
PMID: 19530914
url
https://doi.org/10.1089/hum.2009.025View
Published, Version of Record (VoR) Open

Abstract

Scientific
Plasmid-encoded DNA vaccines appear to be a safe and effective method for delivering antigen; however, the immunogenicity of such vaccines is often suboptimal. Cytokine adjuvants including interleukin (IL)-12, RANTES, granulocyte-macrophage colony-stimulating factor, IL-15, and others have been used to augment the immune response against DNA vaccines. In particular, IL-15 binds to a unique high-affinity receptor, IL-15Rα; is trans -presented to CD8 + T cells expressing the common βγ chain; and has been shown to play a role in the generation, maintenance, and proliferation of antigen-specific CD8 + T cells. In this study, we took the unique approach of using both a cytokine and its receptor as an adjuvant in an HIV-1 vaccine strategy. To study IL-15Rα expression, a unique monoclonal antibody (KK1.23) was generated to confirm receptor expression in vitro . Coimmunization of IL-15 and IL-15Rα plasmids with HIV-1 antigenic plasmids in mice enhanced the antigen-specific immune response 2-fold over IL-15 immunoadjuvant alone. Furthermore, plasmid-encoded IL-15Rα augments immune responses in the absence of IL-15, suggesting its role as a novel adjuvant. Moreover, pIL-15Rα enhanced the cellular, but not the humoral, immune response as measured by antigen-specific IgG antibody. This is the first report describing that IL-15Rα itself can act as an adjuvant by enhancing an antigen-specific T cell response. Uniquely, pIL-15 and pIL-15Rα adjuvants combined, but not the receptor α chain alone, may be useful as a strategy for generating and maintaining memory CD8 + T cells in a DNA vaccine.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biotechnology & Applied Microbiology
Genetics & Heredity
Medicine, Research & Experimental
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